The syndrome of copper deficiency in young pigs includes spontaneous rupture of the heart and of elastic and muscular arteries. It has been the main objective of this project to interpret the cardiovascular abnormalities in terms of the mechanical properties and composition of the connective tissues and of the biogenesis and interrelation of their components. It is intended to apply the knowledge of the pathogenesis of this model of disease toward an understanding of the normal biogenesis and function of connective tissues. The foundation will be laid for the application of the principles established to the exploration of naturally acquired and heritable disorders of connective tissue in man and animals. Specific aims within the overall objective have been to elucidate (1) the biosynthesis of elastin, (2) properties of the elastin monomer, (3) crosslinkage of elastin and collagen, (4) fine structural organization of aortic fibers, and (5) mechanical properties of aortic components in health and disease. The approach is: (a) to maintain copper-deficient pigs as a source of supply of soluble aortic elastin and collagen and of the partially crosslinked fibrous proteins which composed the vessel wall in this disease; (b) to develop in vitro systems for study of the kinetics and intermediates in biosynthesis of these proteins; (c) to characterize the properties and interactions of soluble elastin and collagen and their reactions with other proteins of the intercellular matrix; (d) to establish the crosslink sequence and enzymes responsible for the stabilization of the fibrous proteins; and (e) to correlate the structural organization by electonmicroscopy with the mechanical properties of the diseased vessels.